[Role of lectins in bacterial and malignant disease of the respiratory system].
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Biomedical subjects
Publications and source records attributed to K Roszkowski.
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We report 2 cases of subacute sensory neuropathy (SSN) in small cell cancer of the lung. In both cases motor disturbances were caused by motor neuropathy and neuropathy as well. In both cases we observed altered immunoreactivity of the nervous tissue, suggesting the participation of humoral immunity in the tissue damage.
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The effects of 7 days' chemotherapy with penicillin G, piperacillin, mezlocillin, cephalothin, cefamandole, cefotaxime, gentamicin, amikacin, streptomycin, rifampicin, doxycycline, and clindamycin on local tumor growth and metastatic lung colonization were studied in an experimental tumor model (BALB/c-mouse-sarcoma L-1). The antibiotic dosages administered to mice were calculated on a body weight basis from doses recommended for human therapy. Except for mezlocillin, piperacillin, rifampicin and doxycycline, antibiotic treatment did not significantly influence local tumor growth, lung colonization and immune functions. Whereas mezlocillin exerted positive (tumor suppressive) or negative (tumor promoting) effects depending on the chemotherapy schedule, tumor growth and spread were significantly increased independent of the timing scheme after rifampicin or doxycycline treatment. Since certain immune functions (delayed type hypersensitivity; proliferation of spleen lymphocytes) were significantly suppressed after administration of mezlocillin, rifampicin and doxycycline, a correlation between antimicrobial chemotherapy and tumor progression may be possible.
Radiotherapy in patients with squamous cell lung cancer produced an increase of urinary magnesium and calcium secretion. This is probably due to the cytolysis of malignant cells and shifting of the acid--base balance toward acidity values. This interpretation is justified by the significant correlation between the regression of tumor and increased secretion of the intercellular cation--magnesium.
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A case report is presented of a 29 year old female with an initial diagnosis of a middle-grade malignant lymphoma. The diagnosis was verified basing on clinical symptoms of central nervous system involvement and results of immunological analysis of sampled lymph nodes, tonsils, and spinal fluid. The result of this analysis allowed a high-grade malignant lymphoblastic lymphoma to be diagnosed enabling to start aggressive chemotherapy followed by radiotherapy. A two year complete remission was observed.
It is already known that physiological microflora of the digestive system plays an important role in local immunity. Studies on immunomodulating activity of some autoantibodies have shown that drugs affecting intestinal microflora possess potent immunosuppressive effect on systemic immunity. These observations inspired to recent investigation on the mechanisms of the influence of digestive tract bacteria on the immune system.
Human isolates of Propionibacterium acnes and Staphylococcus saprophyticus could be shown to liberate low molecular weight peptides (MW less than 6.500 D) with immunomodulating activity. FACS analyses of BALB/c-mouse lymphoid cells from the thymus and spleen revealed an enhanced percentage of T-helper cells after peptide administration. Intestinal microflora decontamination of BALB/c-mice considerably reduced immune cell function and lymphatic tissue proliferation. Apparently, lack of peptide production or liberation correlated to immunosuppression. Substitution of peptides (from P. acnes or S. saprophyticus) to decontaminated mice reconstituted immune cell function and proliferation. Cortisone-resistant thymocytes were used as an experimental equivalent of functional cells in the thymus. Thus, cortisone treatment of BALB/c-mice significantly reduced the number of thymocytes, however, administration of microbial peptides restored the thymus population.
The effects of a 7-day chemotherapy with two broad-spectrum beta-lactam antibiotics (imipenem/cilastatin and cefodizime) on the humoral and cellular immune responses in BALB/c-mice were investigated. Antibiotic dosages were calculated on a body weight basis from therapeutical dosages in human medicine. Treatment of experimental mice with imipenem/cilastatin and cefodizime did not influence the production of immunoglobulines (IgM and IgG) nor the delayed type hypersensitivity to oxazolone. In vitro, exposure of human granulocytes to imipenem/cilastatin and cefodizime did not interfere with their phagocytic activity as determined by chemiluminescence assay. Subinhibitory concentrations of both antibiotics modified Staphylococcus aureus and made them more susceptible for granulocyte phagocytosis in chemiluminescence assays.
The in vitro activity of erythromycin and clarithromycin (a new macrolide antibiotic) on clinical bacterial isolates as well as their effects on the cellular and humoral immune responses in BALB/c-mice and on human granulocytes/monocytes was investigated. Treatment of BALB/c-mice for 7 days with these drugs did not influence the delayed type hypersensitivity to oxazolone nor the production of IgG and IgM immunoglobulins. In vitro, exposure of granulocytes to erythromycin resulted in increased phagocytosis only in higher concentrations (20 mcg/ml), whereas clarithromycin enhanced chemiluminescence response of granulocytes in concentrations ranging from 2.5-20 mcg/ml. Subinhibitory concentrations of both substances modified Staphylococcus aureus and made them more susceptible for granulocyte phagocytosis.
The ability of bacteria and bacterial products to modulate the immune response to unrelated antigens is well documented. Propionibacteria are amongst the most potent immunomodulators stimulating cell populations involved in nonspecific resistance. Generally, the activated immune system provides protection from infectious pathogens and malignancies via mechanisms of recognition and elimination. Accordingly, administration of propionibacteria could be shown to be of benefit in the treatment of neoplastic and infectious diseases. Thus, it can be recommended for further clinical investigations.
Adhesion of bacteria and adhesion of tumor cells have much in common, especially the participation of lectins in this process. In the future it might be possible to inhibit the metastatic process into the liver (e.g. during surgical operations of malignant tumors) and bacterial adherence to mucosal linings or plastic devices by blocking of adhesion molecules (lectins) with appropriate glycoconjugates. Initial clinical trials are very promising.
Lipoteichoic acids (LTAs) and related macromolecules (e.g. cell surface substance, CSS; cell surface antigen, CSA; cell surface complex, CSC) are a group of phosphate-containing polymers associated with the cell walls of Gram-positive bacteria (32). They may be considered as surface-reactive antigens (immunogens, biological response modyfiers) as well as membrane components which mediate the attachment of certain bacteria (S. saprophyticus, S. aureus, group A streptococci) to host cell tissues.
Efficacy of second line therapy which included vepesid and adriamycin or vepesid, adriamycin and cis-platin, in small cell lung cancer was studied. Objective remission was seen in 35% of the once more treated patients. Analysis of survival time showed significant prolongation of it in cases treated once more in comparison with a group of patients with progression of the neoplastic process during primary therapy or patients not treated due to relapses of the process. The observed difference was bigger in patients that reacted with a remission to the second line therapy.
Synthesis and expression of cell surface carbohydrates appear to be involved in recognition events associated with tumor invasion and metastasis. Thus, the potential of murine sarcoma L-1 cells to form experimental lung metastases after i.v. injection was assessed after inhibiting tumor cell protein glycosylation with tunicamycin, swainsonine, bromoconduritol, or 1-desoxynojirimycin. Incubation of sarcoma L-1 cells with 0.5 microgram (or above) of these substances/ml medium for 20-24 h significantly inhibited lung colonization. Cytotoxic side effects or additional organ manifestations could not be found. Gas liquid chromatographic examinations of carbohydrates from treated L-1 cells indicated that sugar synthesis was evidently inhibited. These results suggest that specific glycan structures on tumor cells are required for expression of the metastatic phenotype.
Balb/c-mice were intravenously infected with 5 X 10(4) viable cells of Listeria monocytogenes SLCC 4013. Liver, lung and spleen of the animals showed heavy organ colonization 48 h after infection. Pretreatment of experimental animals with staphylococcal lipoteichoic acid (LTA; 2 mg i.p. 7 and 3 days before challenge) significantly reduced the bacterial count in these organs. In vitro, peritoneal macrophages from LTA-treated mice significantly reduced listerial viability as compared to control cells (p less than 0.0025). In vitro, exposure of macrophages from non-treated animals to LTA did not influence their bacterial killing ability.